The Dukes (5-2) had a 22-8 run in the middle of the first half to open an 18-point lead and then made 10 of their final 13 shots, including eight in a row, in the final 10 minutes of the game to keep the Thundering Herd (5-3) at bay.
Mike Lewis II had 15 points and Marcus Weathers 11 for Duquesne, which shot 58 percent, the best in two seasons under coach Keith Dambrot.
C.J. Burks had four 3-pointers and 26 points on 10-of-15 shooting for Marshall.
The Thundering Herd cut the 18-point first-half deficit to 10, 48-38 at the half and got it down to five early in the second half before Duquesne surged ahead. The Dukes led by 16 with 6:21 to play but saw that dwindle to seven with 1:11 remaining before a Hughes dunk and two Carry free throws iced it.
Duquesne, in a stretch of nine-straight games within the Pittsburgh city limits, last played Marshall 40 years ago.